Abstract
Talacotuzumab, a humanized anti-CD123 monoclonal antibody, was evaluated in combination with decitabine in elderly patients with acute myeloid leukemia (AML) not eligible for intensive chemotherapy. A multicenter, phase 2/3 study was initiated to determine the recommended phase 2 dose (RP2D) of talacotuzumab (Part A) followed by an open-label, randomized comparison of talacotuzumab in combination with decitabine versus decitabine alone to assess achievement of complete response (CR) and overall survival (OS) in Part B. Ten patients were enrolled in Part A and 316 in Part B; the results presented here are based on a database lock on January 25, 2018. Part A confirmed the RP2D of talacotuzumab to be 9 mg/kg. In Part B, CR was achieved in 12/80 (15%) patients receiving combination therapy and in 9/82 (11%) patients receiving decitabine alone (odds ratio: 1.4; 95% confidence interval [CI]: 0.6–3.6; p = 0.44). Median (95% CI) OS was 5.36 (4.27–7.95) months for combination therapy versus 7.26 (6.47–8.64) months for decitabine alone (hazard ratio: 1.04; 95% CI: 0.79–1.37; p = 0.78). Combination therapy showed no improvement in efficacy versus decitabine alone, resulting in the Independent Data Monitoring Committee’s recommendation of early termination of enrollment and discontinuation of talacotuzumab treatment.
| Original language | English |
|---|---|
| Pages (from-to) | 62-74 |
| Number of pages | 13 |
| Journal | Leukemia |
| Volume | 35 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2021 |
Access to Document
Other files and links
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Leukemia, Vol. 35, No. 1, 01.2021, p. 62-74.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy
T2 - results from a multicenter, randomized, phase 2/3 study
AU - Montesinos, Pau
AU - Roboz, Gail J.
AU - Bulabois, Claude Eric
AU - Subklewe, Marion
AU - Platzbecker, Uwe
AU - Ofran, Yishai
AU - Papayannidis, Cristina
AU - Wierzbowska, Agnieszka
AU - Shin, Ho Jin
AU - Doronin, Vadim
AU - Deneberg, Stefan
AU - Yeh, Su Peng
AU - Ozcan, Mehmet Ali
AU - Knapper, Steven
AU - Cortes, Jorge
AU - Pollyea, Daniel A.
AU - Ossenkoppele, Gert
AU - Giralt, Sergio
AU - Döhner, Hartmut
AU - Heuser, Michael
AU - Xiu, Liang
AU - Singh, Indrajeet
AU - Huang, Fei
AU - Larsen, Julie S.
AU - Wei, Andrew H.
N1 - Funding Information: Funding The study was sponsored by Janssen Research & Development, LLC. Funding Information: Conflict of interest GJR extended consulting or advisory services to Agios, Amphivena, AstraZeneca, Boehringer Ingelheim, Glax-oSmithKline, Janssen, MEI Pharma, Roche, Shire, Amgen, Astex Pharmaceuticals, Celator, Celgene, Cellectis, CTI, Genoptix, Juno Therapeutics, MedImmune, Novartis, Onconova Therapeutics, Pfizer, Sunesis Pharmaceuticals, received research funding from Abbvie (Inst), Agios (Inst), Astex Pharmaceuticals (Inst), Celgene (Inst), CTI (Inst), Karyopharm Therapeutics (Inst), MedImmune (Inst), MEI Pharma (Inst), Moffitt (Inst), Novartis (Inst), Onconova Therapeutics (Inst) Pfizer (Inst), Sunesis Pharmaceuticals (Inst), Tensha Therapeutics (Inst) and received travel, accommodations and other expenses from AstraZeneca, Shire, Astellas Pharma, Celator, Incyte, Roche, Amphivena, MEI Pharma, Astex Pharmaceuticals, Janssen, Juno Therapeutics. C-EB received support from Amgen, Astellas, Biosafe, Celgene, Chugai, Jazz Pharmaceuticals, Gentium, Gilead, Janssen, Keocyt, Macopharma, Mallinckrodt Pharmaceuticals, MSD, Mundipharma, OrpheliPharm, Pfizer, Pierre Fabre, Sandoz, Sanofi, Spectrum, Takeda, Teva, Therakos, Vifor pharma. MS received research funding from Amgen and Roche. MS received either travel reimbursements or consultant fees from Amgen, Celgene, Pfizer, and Seattle Genetics. UP has received honoraria from Celgene Corporation. AW received honoraria from Celgene. HD provided consultancy services to Agios, Amgen, Astex Pharmaceuticals, Celator, Celgene, Novartis, Roche, Seattle Genetics, Sunesis, and Tolero, and received research funding from Boehringer Ingelheim, Celgene, Novartis, Bristol-Myers Squibb, and Arog Pharmaceuticals research. JC received support from Ariad, Bristol-Myers Squibb, Novartis, and Teva and consultancy support from Ariad, Bristol-Myers Squibb, Novartis, and Pfizer. DAP is a member of advisory boards for Celgene and Pfizer. C.T.J. is an equity holder in Leuchemix Inc GO provided consultancy services to Novartis, Pfizer, Bristol-Myers Squibb, Johnson & Johnson, Sunesis, Celgene, Karypharm, and Amgen, and received research support from Novartis, Johnson & Johnson, Celgene, Immunogene, and Becton Dickinson. AHW provided consultancy services to Novartis, Celgene, Servier, Abbvie, Roche, Amgen, and CTI, and received research funding from Abbvie, Novartis, Celgene, Servier, Ariad, and Amgen. LX, IS, FH, and JSL are employees of Janssen Research and development and may hold company stocks. Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature Limited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Talacotuzumab, a humanized anti-CD123 monoclonal antibody, was evaluated in combination with decitabine in elderly patients with acute myeloid leukemia (AML) not eligible for intensive chemotherapy. A multicenter, phase 2/3 study was initiated to determine the recommended phase 2 dose (RP2D) of talacotuzumab (Part A) followed by an open-label, randomized comparison of talacotuzumab in combination with decitabine versus decitabine alone to assess achievement of complete response (CR) and overall survival (OS) in Part B. Ten patients were enrolled in Part A and 316 in Part B; the results presented here are based on a database lock on January 25, 2018. Part A confirmed the RP2D of talacotuzumab to be 9 mg/kg. In Part B, CR was achieved in 12/80 (15%) patients receiving combination therapy and in 9/82 (11%) patients receiving decitabine alone (odds ratio: 1.4; 95% confidence interval [CI]: 0.6–3.6; p = 0.44). Median (95% CI) OS was 5.36 (4.27–7.95) months for combination therapy versus 7.26 (6.47–8.64) months for decitabine alone (hazard ratio: 1.04; 95% CI: 0.79–1.37; p = 0.78). Combination therapy showed no improvement in efficacy versus decitabine alone, resulting in the Independent Data Monitoring Committee’s recommendation of early termination of enrollment and discontinuation of talacotuzumab treatment.
AB - Talacotuzumab, a humanized anti-CD123 monoclonal antibody, was evaluated in combination with decitabine in elderly patients with acute myeloid leukemia (AML) not eligible for intensive chemotherapy. A multicenter, phase 2/3 study was initiated to determine the recommended phase 2 dose (RP2D) of talacotuzumab (Part A) followed by an open-label, randomized comparison of talacotuzumab in combination with decitabine versus decitabine alone to assess achievement of complete response (CR) and overall survival (OS) in Part B. Ten patients were enrolled in Part A and 316 in Part B; the results presented here are based on a database lock on January 25, 2018. Part A confirmed the RP2D of talacotuzumab to be 9 mg/kg. In Part B, CR was achieved in 12/80 (15%) patients receiving combination therapy and in 9/82 (11%) patients receiving decitabine alone (odds ratio: 1.4; 95% confidence interval [CI]: 0.6–3.6; p = 0.44). Median (95% CI) OS was 5.36 (4.27–7.95) months for combination therapy versus 7.26 (6.47–8.64) months for decitabine alone (hazard ratio: 1.04; 95% CI: 0.79–1.37; p = 0.78). Combination therapy showed no improvement in efficacy versus decitabine alone, resulting in the Independent Data Monitoring Committee’s recommendation of early termination of enrollment and discontinuation of talacotuzumab treatment.
UR - http://www.scopus.com/inward/record.url?scp=85081676423&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41375-020-0773-5
DO - https://doi.org/10.1038/s41375-020-0773-5
M3 - Article
C2 - 32203138
SN - 0887-6924
VL - 35
SP - 62
EP - 74
JO - Leukemia
JF - Leukemia
IS - 1
ER -